Zebrafish studies reveal molecular and cellular determinants of motor asymmetry

2020

Challenge

Being left- or right-handed is a basic human characteristic, but we still do not know how this trait and other ‘motor asymmetries’ are encoded in the brain. However, it is clear that human hand preference is established early during embryonic development and tends to correlate with other motor asymmetries, including foot and eye preferences. Moreover, many studies have reported changes in handedness in individuals with neurodevelopmental disorders, such as autism and schizophrenia. Thus, the development of motor asymmetries is likely an important part of normal brain development, yet it remains poorly understood.

Advance

IRP researchers led by Harold Burgess, Ph.D., used studies of zebrafish to uncover the molecular pathways that generate motor asymmetry in the brain. Zebrafish have small, relatively simple brains that share the same basic organization as the human brain. The researchers discovered that zebrafish have an innate tendency to explore the environment by swimming in a left- or right-ward direction. They also identified a small cluster of neurons in the frontmost part of the zebrafish brain that are responsible for each fish's preference for swimming in a particular direction, and they successfully altered this preference by manipulating the number of these neurons on each side of the brain. Finally, taking advantage of an unexpected gene mutation, the researchers revealed a genetic pathway that generates the fishes’ individual motor preferences during embryonic development.

Impact

Although we have two copies of most genes, for many genes only one copy is essential for normal development. This study reveals that for some genes, the loss of one copy may lead to subtle behavioral changes like a failure to develop motor preferences. This is important because several common neurodevelopmental disorders arise when one copy of a gene has been inactivated. By discovering how motor preferences are encoded in the fish brain, this research provides a strong lead for analyzing how such asymmetries are acquired and maintained in the human brain.

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